The candidate of the proposed Career Development Award is Dr. Adam Maxwell, a biomedical engineer with over 10 years of experience in medical ultrasound research, particularly shock wave lithotripsy and high- intensity focused ultrasound therapy. He has investigated physical interactions of acoustic waves with tissues, developed research and clinical prototype systems, and researched new applications for ultrasound therapies. The purpose of applying for this Career Development Award is for Dr. Maxwell to cultivate the qualities and abilities necessary to be a successful independent researcher and obtain expertise in urolithiasis under the guidance of three experienced mentors, Drs. Michael Bailey, Jonathan Harper, and Hunter Wessells. The University of Washington is a leading research institution at which Dr. Maxwell plans to pursue his research and career development. He will be supported by a collaborative team with expertise in stone management within the Department of Urology and medical ultrasound in the Center for Industrial and Medical Ultrasound at the Applied Physics Laboratory. His proposed research will investigate a potential new treatment for urolithiasis. Urolithiasis is a common disease that affects approximately 1 in 11 individuals during their lifetime and presents a large burden on U.S. healthcare resources. In the last 30 years, management of urinary tract stones has seen the introduction of several novel approaches, including shock wave lithotripsy (SWL), ureteroscopy, and percutaneous nephrolithotomy. SWL is the only noninvasive procedure for stones, but the likelihood of rendering patients stone-free in a single session is considerably lower than other methods, and has declined in newer lithotripters. Development of a more effective lithotripter remains an unmet clinical challenge. While the physical interactions between shocks and stones were not well understood during this technology's clinical introduction, recent research has established the mechanisms of stone fracture in SWL. Based on this work, a novel type of lithotripsy using widely focused bursts of ultrasound rather than shock waves is proposed. Preliminary data shows that burst wave lithotripsy (BWL) is capable of disintegrating stones in as little as 10 seconds. Furthermore, the size of fragments generated during the procedure can be controlled by the ultrasound frequency, potentiating a therapy that produces small fragments easily passed by patients. The goal of this proposal is to create a scientific rationale that will guide the development of burst wave lithotripsy. In particular, this project proposes to investigate the physical interactions of ultrasound bursts with stones and tissue, and use this information to determine therapy parameters. The specific aims of the proposal are: 1) Develop and characterize a suitable ultrasound source for BWL research, 2) Determine the mechanistic interactions leading to stone fracture by BWL, and 3) Identify the mechanical effects of BWL leading to tissue damage. Dr. Maxwell's long-term research goal is to translate this technology into a clinically useful treatment that improves the standard of care for stone management.